Matching Items (4)
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- All Subjects: Brain--Wounds and injuries.
- Creators: Muthuswamy, Jitendran
- Creators: Stabenfeldt, Sarah
Description
Specificity and affinity towards a given ligand/epitope limit target-specific delivery. Companies can spend between $500 million to $2 billion attempting to discover a new drug or therapy; a significant portion of this expense funds high-throughput screening to find the most successful target-specific compound available. A more recent addition to discovering highly specific targets is the application of phage display utilizing single chain variable fragment antibodies (scFv). The aim of this research was to employ phage display to identify pathologies related to traumatic brain injury (TBI), particularly astrogliosis. A unique biopanning method against viable astrocyte cultures activated with TGF-β achieved this aim. Four scFv clones of interest showed varying relative affinities toward astrocytes. One of those four showed the ability to identify reactive astroctyes over basal astrocytes through max signal readings, while another showed a statistical significance in max signal reading toward basal astrocytes. Future studies will include further affinity characterization assays. This work contributes to the development of targeting therapeutics and diagnostics for TBI.
ContributorsMarsh, William (Author) / Stabenfeldt, Sarah (Thesis advisor) / Caplan, Michael (Committee member) / Sierks, Michael (Committee member) / Arizona State University (Publisher)
Created2013
Description
The football helmet is a device used to help mitigate the occurrence of impact-related traumatic (TBI) and minor traumatic brain injuries (mTBI) in the game of American football. The current design methodology of using a hard shell with an energy absorbing liner may be adequate for minimizing TBI, however it has had less effect in minimizing mTBI. The latest research in brain injury mechanisms has established that the current design methodology has produced a helmet to reduce linear acceleration of the head. However, angular accelerations also have an adverse effect on the brain response, and must be investigated as a contributor of brain injury.
To help better understand how the football helmet design features effect the brain response during impact, this research develops a validated football helmet model and couples it with a full LS-DYNA human body model developed by the Global Human Body Modeling Consortium (v4.1.1). The human body model is a conglomeration of several validated models of different sections of the body. Of particular interest for this research is the Wayne State University Head Injury Model for modeling the brain. These human body models were validated using a combination of cadaveric and animal studies. In this study, the football helmet was validated by laboratory testing using drop tests on the crown of the helmet. By coupling the two models into one finite element model, the brain response to impact loads caused by helmet design features can be investigated. In the present research, LS-DYNA is used to study a helmet crown impact with a rigid steel plate so as to obtain the strain-rate, strain, and stress experienced in the corpus callosum, midbrain, and brain stem as these anatomical regions are areas of concern with respect to mTBI.
To help better understand how the football helmet design features effect the brain response during impact, this research develops a validated football helmet model and couples it with a full LS-DYNA human body model developed by the Global Human Body Modeling Consortium (v4.1.1). The human body model is a conglomeration of several validated models of different sections of the body. Of particular interest for this research is the Wayne State University Head Injury Model for modeling the brain. These human body models were validated using a combination of cadaveric and animal studies. In this study, the football helmet was validated by laboratory testing using drop tests on the crown of the helmet. By coupling the two models into one finite element model, the brain response to impact loads caused by helmet design features can be investigated. In the present research, LS-DYNA is used to study a helmet crown impact with a rigid steel plate so as to obtain the strain-rate, strain, and stress experienced in the corpus callosum, midbrain, and brain stem as these anatomical regions are areas of concern with respect to mTBI.
ContributorsDarling, Timothy (Author) / Rajan, Subramaniam D. (Thesis advisor) / Muthuswamy, Jitendran (Thesis advisor) / Oswald, Jay (Committee member) / Mignolet, Marc (Committee member) / Arizona State University (Publisher)
Created2014
Description
Development of post-traumatic epilepsy (PTE) after traumatic brain injury (TBI) is a major health concern (5% - 50% of TBI cases). A significant problem in TBI management is the inability to predict which patients will develop PTE. Such prediction, followed by timely treatment, could be highly beneficial to TBI patients. Six male Sprague-Dawley rats were subjected to a controlled cortical impact (CCI). A 6mm piston was pneumatically driven 3mm into the right parietal cortex with velocity of 5.5m/s. The rats were subsequently implanted with 6 intracranial electroencephalographic (EEG) electrodes. Long-term (14-week) continuous EEG recordings were conducted. Using linear (coherence) and non-linear (Lyapunov exponents) measures of EEG dynamics in conjunction with measures of network connectivity, we studied the evolution over time of the functional connectivity between brain sites in order to identify early precursors of development of epilepsy. Four of the six TBI rats developed PTE 6 to 10 weeks after the initial insult to the brain. Analysis of the continuous EEG from these rats showed a gradual increase of the connectivity between critical brain sites in terms of their EEG dynamics, starting at least 2 weeks prior to their first spontaneous seizure. In contrast, for the rats that did not develop epilepsy, connectivity levels did not change, or decreased during the whole course of the experiment across pairs of brain sites. Consistent behavior of functional connectivity changes between brain sites and the "focus" (site of impact) over time was demonstrated for coherence in three out of the four epileptic and in both non-epileptic rats, while for STLmax in all four epileptic and in both non-epileptic rats. This study provided us with the opportunity to quantitatively investigate several aspects of epileptogenesis following traumatic brain injury. Our results strongly support a network pathology that worsens with time. It is conceivable that the observed changes in spatiotemporal dynamics after an initial brain insult, and long before the development of epilepsy, could constitute a basis for predictors of epileptogenesis in TBI patients.
ContributorsTobin, Edward (Author) / Iasemidis, Leonidas (Thesis advisor) / Tsakalis, Konstantinos (Committee member) / Muthuswamy, Jitendran (Committee member) / Arizona State University (Publisher)
Created2012
Description
Pediatric traumatic brain injury (TBI) is a leading cause of death and disability in children. When TBI occurs in children it often results in severe cognitive and behavioral deficits. Post-injury, the pediatric brain may be sensitive to the effects of TBI while undergoing a number of age-dependent physiological and neurobiological changes. Due to the nature of the developing cortex, it is important to understand how a pediatric brain recovers from a severe TBI (sTBI) compared to an adult. Investigating major cortical and cellular changes after sTBI in a pediatric model can elucidate why pediatrics go on to suffer more neurological damage than an adult after head trauma. To model pediatric sTBI, I use controlled cortical impact (CCI) in juvenile mice (P22). First, I show that by 14 days after injury, animals begin to show recurrent, non-injury induced, electrographic seizures. Also, using whole-cell patch clamp, layer V pyramidal neurons in the peri-injury area show no changes except single-cell excitatory and inhibitory synaptic bursts. These results demonstrate that CCI induces epileptiform activity and distinct synaptic bursting within 14 days of injury without altering the intrinsic properties of layer V pyramidal neurons. Second, I characterized changes to the cortical inhibitory network and how fast-spiking (FS) interneurons in the peri-injury region function after CCI. I found that there is no loss of interneurons in the injury zone, but a 70% loss of parvalbumin immunoreactivity (PV-IR). FS neurons received less inhibitory input and greater excitatory input. Finally, I show that the cortical interneuron network is also affected in the contralateral motor cortex. The contralateral motor cortex shows a loss of interneurons and loss of PV-IR. Contralateral FS neurons in the motor cortex synaptically showed greater excitatory input and less inhibitory input 14 days after injury. In summary, this work demonstrates that by 14 days after injury, the pediatric cortex develops epileptiform activity likely due to cortical inhibitory network dysfunction. These findings provide novel insight into how pediatric cortical networks function in the injured brain and suggest potential circuit level mechanisms that may contribute to neurological disorders as a result of TBI.
ContributorsNichols, Joshua (Author) / Anderson, Trent (Thesis advisor) / Newbern, Jason (Thesis advisor) / Neisewander, Janet (Committee member) / Qiu, Shenfeng (Committee member) / Stabenfeldt, Sarah (Committee member) / Arizona State University (Publisher)
Created2015